Kosmider B, Osiecka R, Zyner E, Ochocki J
Department of Cytogenetics and Plant Molecular Biology, University of Lodz, Lodz, Poland.
Drug Chem Toxicol. 2005;28(2):231-44. doi: 10.1081/dct-52555.
cis-bis(3-aminoflavone)dichloroplatinum(II) [cis-Pt(II) complex of 3-aminoflavone] is an analog of cis-DDP characterized by low cytotoxicity and anticancer properties in vivo. In order to evaluate genotoxic properties of this chemical compound, the comet assay in human lymphocytes was used. The analysis of DNA damage after 1-h cell incubation with cis-Pt(II) complex of 3-aminoflavone and cis-DDP was carried out, and DNA repair kinetics were evaluated after 0.5-h, 1-h, and 1.5-h postexposure incubation. It has been shown that cis-Pt(II) complex of 3-aminoflavone causes the increase in tail moments in comparison with cis-DDP. On the other hand, the decrease in these values caused by cis-DDP was connected mainly with the presence of DNA and DNA-protein crosslinks. The decrease in tail moments after cis-Pt(II) complex of 3-aminoflavone lymphocyte treatment was already observed after 0.5-h postexposure incubation, whereas in the variant with hydrogen peroxide application these values after cis-Pt(II) complex of 3-aminoflavone addition were higher in comparison with cis-DDP. Results obtained on the basis of the comet assay could confirm the occurrence of DNA breaks and cross-links induced by cis-Pt(II) complex of 3-aminoflavone.
顺式双(3-氨基黄酮)二氯铂(II)[3-氨基黄酮的顺式铂(II)配合物]是顺铂的类似物,其特点是体内细胞毒性低且具有抗癌特性。为了评估该化合物的遗传毒性,采用了人淋巴细胞彗星试验。对人淋巴细胞与3-氨基黄酮的顺式铂(II)配合物和顺铂孵育1小时后的DNA损伤进行了分析,并在暴露后孵育0.5小时、1小时和1.5小时后评估了DNA修复动力学。结果表明,与顺铂相比,3-氨基黄酮的顺式铂(II)配合物会导致尾矩增加。另一方面,顺铂导致这些值降低主要与DNA和DNA-蛋白质交联的存在有关。在暴露后孵育0.5小时后,就已观察到用3-氨基黄酮的顺式铂(II)配合物处理淋巴细胞后尾矩降低,而在应用过氧化氢的变体中,添加3-氨基黄酮的顺式铂(II)配合物后的这些值比顺铂更高。基于彗星试验获得的结果可以证实3-氨基黄酮的顺式铂(II)配合物会诱导DNA断裂和交联。